The purpose of this project is to conduct the coordinate interdisciplinary studies on high-risk populations in order to clarify the role of genetic mechanisms and host-environmental interactions in carcinogenesis. Clinical studies of high-risk families have suggested etiologic relationships between the premalignant dysplastic nevus syndrome and cutaneous melanoma, both hereditary and sporadic types. Mechanisms of host sysceptibility are seen in DNA repair defects in familial melanoma, and in families prone to sarcomas and other rare cancers. Investigative laboratory collaborations have clarified the relationship between lifestyle, subclinical immunologic perturbations and the epidemic of Acquired Immunodeficiency Syndrome in male homosexuals and other high risk groups. Seroepidemiologic studies of the newly discovered condidate human leukemia retrovirus, HTLV, have defined patterns of virus infection and disease relationships. Studies of leukemias and other cancers as second primary malignancies due to exposures to therapeutic agents have quantified the risk of a variety of chemotherapy and radiation exposures.